Acidic pH Restricts Non-Tuberculous Mycobacteria Replication.

IF 3.1 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Microbiology Pub Date : 2026-03-08 DOI:10.1111/mmi.70060

Parise K Lockwood,Luiz Pedro Sorio de Carvalho,Rachel P J Lai,Maximiliano G Gutierrez

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引用次数: 0

Abstract

Non-tuberculous mycobacteria (NTM) are becoming increasingly prevalent in clinical settings with certain environmental species becoming opportunistic in both immunocompetent and immunodeficient hosts. However, the factors that drive this environmental-to-opportunistic switch remain poorly understood. NTM are environmental organisms that commonly thrive in acidic niches. Conversely, in host cells, acidic pH acts as a defence mechanism. Here, we investigated how acidic pH impacts NTM replication both in vitro and in cellulo. A set of 12 NTM, representing both environmental and opportunistic bacteria, was assessed for growth across a pH range of 4.5-8.0 in vitro, revealing that acid tolerance was species specific. Fluorescent NTM reporters were generated and used to track real-time live cell intracellular replication within human macrophages where acid tolerant species in vitro replicated with a higher efficiency in cellulo than acid sensitive NTM. Further neutralisation of the phagosomal pH using bafilomycin A1 (BafA1) led to enhanced intracellular replication and survival of NTM. This study demonstrated that specific environmental adaptations may determine the opportunistic potential of NTM whilst acidic pH within the host serves as a key host defence mechanism to restrict NTM growth.

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酸性pH值限制非结核分枝杆菌的复制。

非结核分枝杆菌（NTM）在临床环境中变得越来越普遍，某些环境物种在免疫正常和免疫缺陷宿主中都变得机会性。然而，推动这种从环境到机会主义的转变的因素仍然知之甚少。NTM是一种环境生物，通常在酸性生态位中茁壮成长。相反，在宿主细胞中，酸性pH值作为一种防御机制。在这里，我们研究了酸性pH值如何影响NTM在体外和细胞内的复制。一组代表环境细菌和机会细菌的12种NTM在体外pH范围为4.5-8.0的条件下进行了生长评估，结果表明耐酸性是物种特异性的。产生了荧光NTM报告细胞，并用于跟踪人巨噬细胞内活细胞的实时复制，其中耐酸物种在细胞内的体外复制效率高于酸敏感的NTM。使用巴菲霉素A1 （BafA1）进一步中和吞噬体pH可增强NTM的细胞内复制和存活。该研究表明，特定的环境适应可能决定了NTM的机会潜力，而宿主体内的酸性pH值是限制NTM生长的关键宿主防御机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Microbiology 生物-生化与分子生物学

CiteScore

7.20

自引率

5.60%

发文量

132

审稿时长

1.7 months

期刊介绍： Molecular Microbiology, the leading primary journal in the microbial sciences, publishes molecular studies of Bacteria, Archaea, eukaryotic microorganisms, and their viruses. Research papers should lead to a deeper understanding of the molecular principles underlying basic physiological processes or mechanisms. Appropriate topics include gene expression and regulation, pathogenicity and virulence, physiology and metabolism, synthesis of macromolecules (proteins, nucleic acids, lipids, polysaccharides, etc), cell biology and subcellular organization, membrane biogenesis and function, traffic and transport, cell-cell communication and signalling pathways, evolution and gene transfer. Articles focused on host responses (cellular or immunological) to pathogens or on microbial ecology should be directed to our sister journals Cellular Microbiology and Environmental Microbiology, respectively.